A5039070300- Malaria Research and Control
- Computational Drug Discovery Methods
- Synthesis and Catalytic Reactions
- HIV/AIDS drug development and treatment
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Synthesis of Tetrazole Derivatives
- Synthesis and biological activity
- Nuclear Receptors and Signaling
- Chemical Synthesis and Analysis
- Marine Sponges and Natural Products
- Endoplasmic Reticulum Stress and Disease
- Research on Leishmaniasis Studies
- Bioactive Compounds and Antitumor Agents
- RNA modifications and cancer
- Traditional and Medicinal Uses of Annonaceae
- Microbial Natural Products and Biosynthesis
- Microtubule and mitosis dynamics
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Phenothiazines and Benzothiazines Synthesis and Activities
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Histone Deacetylase Inhibitors Research
University of Naples Federico II
2015-2025
Consorzio Interuniversitario Nazionale per l'Informatica
2020
Istituto Nazionale di Fisica Nucleare, Sezione di Napoli
2015
Istituto di Farmacologia Traslazionale
2015
University of Milan
2008-2014
Zero to Three
2014
Marche Polytechnic University
2010
University of Bologna
2009
University of Siena
2005-2008
Istituti di Ricovero e Cura a Carattere Scientifico
2008
We reported previously that Bcl-2 is paradoxically down-regulated in paclitaxel-resistant cancer cells. reveal here paclitaxel directly targets the loop domain, thereby facilitating initiation of apoptosis. Molecular modeling revealed an extraordinary similarity between binding sites and beta-tubulin, leading us to speculate could be mimetic endogenous peptide ligand, which binds both proteins. tested hypothesis mimics Nur77, which, like paclitaxel, changes function Bcl-2. This premise was...
Malaria is a major health problem in poverty-stricken regions where new antiparasitic drugs are urgently required at an affordable price. We report herein the design, synthesis, and biological investigation of novel antimalarial agents with low potential to develop resistance structurally based on highly conjugated scaffold. Starting from hit, designed modifications were performed hypothesizing specific interaction free heme generation radical intermediates. This approach provided...
Hepatitis C virus (HCV) infection is an emerging global epidemic, and no effective cure yet available. Interferon-α (INFα) pegylated INFs, in combination or otherwise with ribavirin, have proven to be more than 50% of chronically infected patients. New better therapeutic strategies are therefore needed. HCV nonstructural protein 3 (NS3) RNA helicase (h) a promising target for developing new therapeutics. QU663 was discovered as potent selective inhibitor the reaction NS3 (Ki = 0.75 μM),...
Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortis simplex, showing submicromolar activity against chloroquine-resistant strains of Plasmodium falciparum. Using plakortin as novel antimalarial hit, we have prepared series semisynthetic derivatives in order to gain insights into structural requirements 1,2-dioxanes for exhibiting activity. Their synthesis, spectroscopic and computational analysis, vitro are herein reported. Results...
The new endoperoxyketal polyketides manadoperoxides A−D (2−5) have been isolated from the Indonesian sponge Plakortis cfr. simplex and their stereostructures established by means of spectroscopic data semisynthetic transformations. Manadoperoxides were assayed in vitro against D10 W2 strains Plasmodium falciparum showed moderate antimalarial activity compared to that plakortin (1) peroxyplakoric B3 ester (9), latter differing manadoperoxide B only minor structural details. This unexpected...
Decreased proteasome activity is a hallmark of brain and retinal neurodegenerative diseases (Alzheimer's, Parkinson's diseases, glaucoma) boosting the search for molecules acting as activators. Based on hypothesis an electrostatic key code driving catalytic core particle (20S) activation by regulatory particles (RPs), we identified tetra-anionic meso-Tetrakis(4-sulphonatophenyl)-porphyrin (H2TPPS) new activator human proteasome. By means integrated approach, including bioinformatics,...
Antimalarial agents structurally based on novel pharmacophores, synthesized by low-cost synthetic procedures and characterized low potential for developing resistance are urgently needed. Recently, we developed an innovative class of antimalarials a polyaromatic pharmacophore. Hybridizing the 4-aminoquinoline or 9-aminoacridine system known with clotrimazole-like pharmacophore, polyarylmethyl group, describe herein development unique (4a-l 5a-c) selectively interacting free heme interfering...
Protein conformational fluctuations are critical for biological functions, although the relationship between protein motion and function has yet to be fully explored. By a thorough bioinformatics analysis of cholinesterases (ChEs), we identified specific hot spots, responsible those active-site residues that play role in modulating cooperative network among key substructures. This drew optimization our design strategy discover potent reversible inhibitors human acetylcholinesterase...
Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds evaluated their vitro inhibitory activity against 11 human HDACs isoforms. After identification of "hit" molecule, programmed variation at cap group and linker was carried out order increase inhibition and/or paralogue selectivity. Some derivatives showed increased number isoforms, even if overall range...
An acyclic pyrimidine analogue, containing a five-member cycle fused on the ring, was synthesized and introduced at position 7 or 12 of 15-mer oligodeoxynucleotide GGTTGGTGTGGTTGG, known as thrombin-binding aptamer (TBA). Characterization by 1H NMR CD spectroscopies resulting aptamers, TBA-T7b TBA-T12b, showed their ability to fold into typical antiparallel chairlike G-quadruplex structure formed TBA. The apparent melting temperatures indicated that introduction residue, mainly 7, improves...
Class III β-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing incorporation GBP1 GTPase into microtubules. Once cytoskeleton, binds prosurvival kinases such as PIM1 and initiates signaling pathway that induces paclitaxel. Therefore, inhibition GBP1:PIM1 interaction could potentially revert A panel 44 4-azapodophyllotoxin derivatives was screened NCI-60 cell panel. The result is 31 are active comparative analysis demonstrated specific activity...
Abstract A broad biophysical analysis was performed to investigate the molecular basis of neuroprotective action Curcuma longa extracts in Alzheimer’s disease. By combining circular dichroism and electron paramagnetic resonance experiments with modeling calculations, minor components extracts, such as demethoxycurcumin ( 2 , DMC), bisdemethoxycurcumin 3 BDMC) cyclocurcumin 4 CYC), were analyzed a membrane environment mimicking phospholipid bilayer. Our study provides first evidence on...
The chemical analysis of the sponge Dysidea avara afforded known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore role thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted avarone into derivative thiazoavarone. semisynthetic compound, well natural metabolites avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual asexual stages Plasmodium falciparum,...
Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis investigation active site gorge topology butyrylcholinesterase (BuChE) acetylcholinesterase (AChE) by using flexible docking procedures, molecular modeling studies formulated hypothesis extra interaction sites in hBuChE, namely, a mid-gorge peripheral site. The design strategy led to BuChE inhibitors, balancing potency selectivity. Among compounds identified, ligand 4m, containing...
We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole easy synthesize by low-cost synthetic procedures. SAR delineated number structural features able modulate in vitro vivo activity. A selected set antimalarials was further biologically investigated displayed low toxicity panel human murine cell lines. In vitro,...
The synthesis and the biological characterization of novel highly selective pyrroloquinoxaline 5-HT3 receptor (5-HT3R) ligands are described. In functional in vivo studies quinoxalines modulated cardiac parameters by direct interaction with myocardial 5-HT3Rs. potent 5-HT3R 4h 4n modulate chronotropy (right atrium) but not inotropy (left at level, being antagonist partial agonist, respectively. Preliminary pharmacokinetic indicate that (S)-4n 4a, representatives ligands, possess poor...
A multidisciplinary approach, based on molecular dynamics/mechanics, ab initio calculations, dynamic docking studies, and chemical reactions, has been employed to gain insight into the mechanism of antimalarial action plakortin dihydroplakortin, simple 1,2-dioxanes isolated from sponge Plakortis simplex. Our results show that these molecules, after interaction endoperoxide bond with Fe(ii), likely coming heme molecule, give rise formation an oxygen radical, followed by rearrangement a carbon...
Optically pure modified acyclic nucleosides offer unique advantages in exploring the effect on thrombin inhibition of single residue modifications at key positions TBA.
Three homologous cationic porphyrins differently affect the 20S proteasome gating mechanism.
Chiral natural compounds are often biosynthesized in an enantiomerically pure fashion, and stereochemistry plays a pivotal role biological activity. Herein, we investigated the significance of chirality for nature-inspired 3-Br-acivicin (3-BA) its derivatives. The three unnatural isomers 3-BA ester amide derivatives were prepared characterized their antimalarial Only (5
Pyrrolobenzoxazepinones (PBOs) represent a new class of human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) whose prototype is 5. Molecular modeling studies based on the X-ray structures HIV-1 RT prompted synthesis novel analogues which were tested as anti-HIV agents. The PBO derivatives specifically designed to target highly conserved amino acid residues within β12-β13 hairpin, namely primer grip, proved be very potent against most common...
Identification of new molecular scaffolds structurally unrelated to known antimalarials may represent a valid strategy overcome resistance P. falciparum (Pf) currently available drugs. We describe herein the investigation polycyclic pharmacophore, related clotrimazole, develop innovative antimalarial agents. This study allowed us discover compounds characterized by high in vitro potency, particularly against Pf CQ-resistant strains selectively targeting free heme, which are easy synthesize...